The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

  • See Evidence submitted by expert panel for details.

Variant: NM_000314.7(PTEN):c.599T>C (p.Phe200Ser)

CA000532

189414 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: 633ec420-0afb-4647-b05d-ed0a118f2469

HGVS expressions

NM_000314.7:c.599T>C
NM_000314.7(PTEN):c.599T>C (p.Phe200Ser)
NC_000010.11:g.87952224T>C
CM000672.2:g.87952224T>C
NC_000010.10:g.89711981T>C
CM000672.1:g.89711981T>C
NC_000010.9:g.89701961T>C
NG_007466.2:g.93786T>C
NM_000314.5:c.599T>C
NM_000314.6:c.599T>C
NM_001304717.2:c.1118T>C
NM_001304718.1:c.8T>C
NM_001304717.5:c.1118T>C
NM_001304718.2:c.8T>C
NM_000314.8:c.599T>C
ENST00000371953.7:c.599T>C
ENST00000472832.2:n.26T>C

Uncertain Significance

Met criteria codes 3
PP2 PM2 PS4_Moderate
Not Met criteria codes 19
PS2 PS3 PS1 BA1 PP1 PP3 PM1 PM4 PM5 PM6 PVS1 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP4

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.599T>C (p.Phe200Ser) is currently classified as a variant of uncertain significance for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PM2: Absent in large sequenced populations (PMID 27535533). PS4_M: Probands with phenotype specificity score of 2-3.5. (internal laboratory contributor SCV000222124.11) PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
Met criteria codes
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
absent gnomAD
PS4_Moderate
GDX1: child with extreme macrocephaly, DD, other neuro features, peds score = 5 = 1 PS4 point. GDX2: child with non-extreme macrocephaly, dev delay, lipoma vs. AVM, hemangioma, peds score minimum = 6 = 1 PS4 point.

Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
GDX1/Invitae/Eng lab shared family: variant present in proband with macrocephaly, dev delay, penile freck; father with macrocephaly, lipomas, hemangioma, oral papillomas, polyps and pat uncle with lipomas and polyps. Also unaffected PGM and her mother with breast cancer dx 80. Per VCEP review count 2 meioses (proband, dad, pat uncle).
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2020-03-23
Published on: 2020-03-26
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